Vitamin B12 Deficiency: Symptoms, Causes, Treatment

Vitamin B12 Deficiency;

Skin pigmentation in vitamin b12 Deficiency - Modern HealthMe, Healthline, WebMD
Skin Pigmentation in Vitamin B12 Deficiency


Vitamin B12, also known as cobalamin, is a vital nutrient that plays a Important role in many bodily functions, including red blood cell formation, neurological function, and DNA synthesis.

However, deficiency in this vitamin can lead to various health problems, ranging from fatigue to neurological disorders.

Causes of Vitamin B12 Deficiency

  1. Poor Dietary Intake: Not consuming enough foods rich in vitamin B12, such as meat, fish, eggs, and dairy products.
  2. Malabsorption: Conditions like pernicious anemia, celiac disease, or Crohn’s disease can hinder the absorption of vitamin B12 from food.
  3. Medications: Certain medications, such as proton pump inhibitors (PPIs) or metformin, can interfere with vitamin B12 absorption.
  4. Surgical Procedures: Surgeries that involve the removal of parts of the stomach or intestines can affect vitamin B12 absorption.
  5. Other causes – Other damage to the small intestine, such as inflammation from celiac disease or infection with the tapeworm Diphyllobothrium latum, may also result in a B12 deficiency.

Signs and Symptoms of Vitamin B12 Deficiency:

1. Fatigue

  • Feeling tired or weak, even after getting enough rest.
  • You may lack energy to do daily activities.

2. Pale or Jaundiced Skin

  • Paleness of the skin, especially noticeable on the face and hands.
  • Yellowing of the skin and whites of the eyes (jaundice) due to decreased red blood cell production.

3. Neurological Symptoms

  • Tingling or numbness in the hands and feet.
  • Difficulty walking or maintaining balance.
  • Memory problems or difficulty concentrating.

4. Skin Hyperpigmentation: Hyperpigmentation with generalized weakness may be the initial presentation of several systemic conditions. Vit. B12 deficiency can present very rarely as hyperpigmentation

5. Mood Changes

  • Feelings of depression or sadness.
  • Irritability or mood swings.
  • Anxiety or nervousness.

6. Digestive Issues

  • Loss of appetite or changes in taste.
  • Diarrhea or constipation.
  • Nausea or vomiting.

7. Weakness and Muscle Soreness

  • Weakness in muscles, making it difficult to perform physical tasks.
  • Muscle soreness or aches, especially after minimal exertion.


Suspicion of vitamin B12 Deficiency after taking clinical history and examining the patient, we must confirm the diagnosis with the help of following:

1. Initial Lab Tests:

  • Complete Blood Count (CBC) with Peripheral Smear
  • Serum B12 and Folate Levels

2. CBC Findings:

  • Anemia: Decreased Hemoglobin and Hematocrit
  • Macrocytic Anemia: Increased Mean Corpuscular Volume (MCV) (>100)
  • Peripheral Blood Smear: Hypersegmented Neutrophils

3. Serum B12 and Folate Levels:

  • B12 Levels:
    • Normal: >300 pg/mL
    • Borderline: 200-300 pg/mL
    • Deficient: <200 pg/mL
  • Differentiating B12 and Folate Deficiency: Both Tested

4. Further Testing for Borderline B12 Levels:

  • Enzymatic Testing:
    • Methylmalonic Acid (MMA) Levels
    • Homocysteine Levels

5. Confirmation of B12 Deficiency:

  • Elevated MMA and Homocysteine Levels

6. Etiology Investigation:

  • Surgical History:
    • Gastrectomy
    • Resection of Terminal Ileum
    • Gastric Bypass
  • GI Workup:
    • Malabsorption Causes (Crohn’s, Celiac Disease)
  • Dietary Factors:
    • Strict Vegan Diet
  • Autoimmune Conditions:
    • Testing for Anti-Intrinsic Factor Antibodies

7. Former Diagnostic Test (No Longer Used):

  • Schilling Test:
    • Radiolabeled B12 Absorption Test
    • Diagnosis of Pernicious Anemia

Peripheral Smear (PS) Findings:

When examining a peripheral blood smear, certain abnormalities may indicate vitamin B12 deficiency:

  1. Hypersegmented Neutrophils:
  • Neutrophils are a type of white blood cell involved in fighting infection.
  • In B12 deficiency, some neutrophils may have more lobes than normal. Normally, neutrophils have 2-3 lobes, but in B12 deficiency, they may have 5 or more lobes.
  • This condition is called hypersegmentation, and it’s a characteristic feature of B12 deficiency observed in the peripheral blood smear.
  • The presence of hypersegmented neutrophils suggests impaired DNA synthesis due to B12 deficiency, resulting in delayed maturation of neutrophils in the bone marrow.
  • Hypersegmented neutrophils are not specific to B12 deficiency but are highly suggestive when combined with other clinical and laboratory findings.

Risk Factors

  1. Age: Older adults are at higher risk due to decreased stomach acid production and potential absorption issues.
  2. Vegetarian or Vegan Diet: Limited intake of animal products can lead to lower vitamin B12 levels.
  3. Digestive Disorders: Conditions like celiac disease or inflammatory bowel disease can affect nutrient absorption.
  4. Gastrointestinal Surgery: Procedures that alter the digestive tract can impact vitamin B12 absorption.

Treatment Of Vitamin B12 Deficiency:

Treatment of vitamin B12 deficiency aims at replenishing B12 levels, with the approach varying based on the underlying cause:

1. Strict Vegan Diet:

  • Oral B12 supplement is sufficient for repletion.

2. Intrinsic Factor Deficiency (Pernicious Anemia, Gastric Bypass Surgery):

  • Parenteral administration of B12 is necessary due to impaired absorption.
  • Intramuscular injection of 1000 mcg B12 once monthly is recommended.
  • For newly diagnosed patients, 1000 mcg B12 is given intramuscularly once weekly for four weeks, followed by monthly dosing.

3. Alternative Route for B12 Absorption:

  • Studies suggest high oral doses can saturate intestinal B12 receptors, making oral B12 effective despite intrinsic factor deficiency.

4. Monitoring and Prophylaxis:

  • Patients at risk, such as those with Crohn’s or celiac disease, should undergo routine B12 monitoring.
  • Treatment initiation occurs when B12 levels decline with worsening disease severity. Prophylactic treatment before B12 levels fall is not recommended.

Differential Diagnosis:

Vitamin B12 deficiency shares symptoms with several other conditions, including:

  • Lead toxicity
  • Syphilis
  • HIV myelopathy
  • Multiple sclerosis

These conditions should be considered during diagnosis to ensure appropriate treatment and management.

Complications of Vitamin B12 Deficiency:

1. Anemia:

  • Vitamin B12 deficiency can lead to megaloblastic anemia, characterized by larger-than-normal red blood cells. This can result in fatigue, weakness, and pale skin.

2. Neurological Disorders:

  • Without enough vitamin B12, the protective covering of nerve fibers (myelin) can deteriorate, leading to neurological complications such as numbness and tingling in the hands and feet, difficulty walking, memory loss, and cognitive impairment.

3. Cardiovascular Issues:

  • Elevated levels of homocysteine, a byproduct of B12 deficiency, can increase the risk of cardiovascular diseases such as heart attacks and strokes.

4. Psychiatric Symptoms:

  • Vitamin B12 deficiency has been associated with mood disorders such as depression and anxiety, as well as cognitive decline and dementia.

5. Neuropsychiatric Disorders:

  • Severe and prolonged B12 deficiency can lead to irreversible damage to the nervous system, resulting in conditions like peripheral neuropathy, which causes numbness, tingling, and muscle weakness.

6. Hyperpigmentation:

  • Hyperpigmentation, or darkening of the skin, can occur in vitamin B12 deficiency due to changes in melanin production.

7. Gastrointestinal Complications:

  • Vitamin B12 deficiency can result in gastrointestinal issues such as glossitis (inflammation of the tongue), mouth ulcers, and digestive problems.

8. Vision Impairment:

  • In rare cases, vitamin B12 deficiency may contribute to vision problems, including optic neuropathy, which can lead to vision loss if left untreated.

9. Increased Susceptibility to Infections:

  • A weakened immune system due to vit. B12 deficiency may make individuals more susceptible to infections and illnesses.

Vitamin B12 deficiency is a serious health concern that can lead to various complications if left untreated.

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